IDENTIFICATION OF A VITAMIN-D RECEPTOR HOMODIMER-TYPE RESPONSE ELEMENT IN THE RAT CALCITRIOL 24-HYDROXYLASE GENE PROMOTER

Calcitriol (1,25 dihydroxyvitamin D-3, VD) controls multiple aspects o f homeostasis, cell growth and differentiation by the action of its nu clear receptor (VDR), which binds to, and activates transcription from , response elements in the promoter region of its target genes. One of these target genes is calcitriol 24 hydroxylase, an enzyme that initi ates the degradation of 25-dihydroxyvitamin D-3 (calcidiol) and calcit riol. We screened the promoter of rat calcitriol 24-hydroxylase for po tential VDR binding sites and identified a functional VD response elem ent, between positions -250 and -233. This response element consists o f two directly repeated hexameric core binding motifs spaced by six nu cleotides and confers VD dependent transactivation mediated by VDR hom odimers or alternatively by heterodimers formed by VDR and retinoic ac id receptor (RAR). Its structure and function are very similar to thos e of the homodimer type response element of the human osteocalcin prom oter. (C) 1994 Academic Press, Inc.